ID E2AK2_HUMAN Reviewed; 551 AA. AC P19525; A8K3P0; D6W584; E9PC80; Q52M43; Q7Z6F6; Q9UIR4; DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1991, sequence version 2. DT 27-MAR-2024, entry version 252. DE RecName: Full=Interferon-induced, double-stranded RNA-activated protein kinase; DE EC=2.7.11.1; DE AltName: Full=Eukaryotic translation initiation factor 2-alpha kinase 2; DE Short=eIF-2A protein kinase 2; DE AltName: Full=Interferon-inducible RNA-dependent protein kinase; DE AltName: Full=P1/eIF-2A protein kinase; DE AltName: Full=Protein kinase RNA-activated; DE Short=PKR; DE Short=Protein kinase R {ECO:0000303|PubMed:11438532}; DE AltName: Full=Tyrosine-protein kinase EIF2AK2; DE EC=2.7.10.2; DE AltName: Full=p68 kinase; GN Name=EIF2AK2; Synonyms=PKR, PRKR; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 101-118 AND RP 309-325, AND INDUCTION. RX PubMed=1695551; DOI=10.1016/0092-8674(90)90374-n; RA Meurs E., Chong K., Galabru J., Thomas N.S.B., Kerr I.M., Williams B.R.G., RA Hovanessian A.G.; RT "Molecular cloning and characterization of the human double-stranded RNA- RT activated protein kinase induced by interferon."; RL Cell 62:379-390(1990). RN [2] RP SEQUENCE REVISION. RA Meurs E.; RL Submitted (AUG-1990) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1373553; DOI=10.1016/0042-6822(92)90732-5; RA Thomis D.C., Doohan J.P., Samuel C.E.; RT "Mechanism of interferon action: cDNA structure, expression, and regulation RT of the interferon-induced, RNA-dependent P1/eIF-2 alpha protein kinase from RT human cells."; RL Virology 188:33-46(1992). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1). RX PubMed=8921913; DOI=10.1016/0378-1119(96)00314-9; RA Kuhen K.L., Shen X., Samuel C.E.; RT "Mechanism of interferon action sequence of the human interferon-inducible RT RNA-dependent protein kinase (PKR) deduced from genomic clones."; RL Gene 178:191-193(1996). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Placenta; RX PubMed=8812437; DOI=10.1006/geno.1996.0446; RA Kuhen K.L., Shen X., Carlisle E.R., Richardson A.L., Weier H.-U.G., RA Tanaka H., Samuel C.E.; RT "Structural organization of the human gene (PKR) encoding an interferon- RT inducible RNA-dependent protein kinase (PKR) and differences from its mouse RT homolog."; RL Genomics 36:197-201(1996). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9726442; DOI=10.1089/jir.1998.18.609; RA Xu Z., Williams B.R.; RT "Genomic features of human PKR: alternative splicing and a polymorphic CGG RT repeat in the 5'-untranslated region."; RL J. Interferon Cytokine Res. 18:609-616(1998). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RA Li H., Huang F., Shen C., Zhou G., Zheng G., Ke R., Lin L., Yang S.; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain, and Embryo; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [13] RP PROTEIN SEQUENCE OF 2-18; 27-40; 70-77; 414-426 AND 430-440, CLEAVAGE OF RP INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Prostatic carcinoma; RA Bienvenut W.V., Gao M., Leug H.; RL Submitted (JUN-2009) to UniProtKB. RN [14] RP INTERACTION WITH DNAJC3. RX PubMed=8576172; DOI=10.1074/jbc.271.3.1702; RA Polyak S.J., Tang N., Wambach M., Barber G.N., Katze M.G.; RT "The P58 cellular inhibitor complexes with the interferon-induced, double- RT stranded RNA-dependent protein kinase, PKR, to regulate its RT autophosphorylation and activity."; RL J. Biol. Chem. 271:1702-1707(1996). RN [15] RP INTERACTION WITH HIV-1 TAT. RX PubMed=9079663; DOI=10.1074/jbc.272.13.8388; RA Brand S.R., Kobayashi R., Mathews M.B.; RT "The Tat protein of human immunodeficiency virus type 1 is a substrate and RT inhibitor of the interferon-induced, virally activated protein kinase, RT PKR."; RL J. Biol. Chem. 272:8388-8395(1997). RN [16] RP INTERACTION WITH HCV NON-STRUCTURAL PROTEIN 5A (MICROBIAL INFECTION). RX PubMed=9143277; DOI=10.1006/viro.1997.8493; RA Gale M.J. Jr., Korth M.J., Tang N.M., Tan S.-L., Hopkins D.A., Dever T.E., RA Polyak S.J., Gretch D.R., Katze M.G.; RT "Evidence that hepatitis C virus resistance to interferon is mediated RT through repression of the PKR protein kinase by the nonstructural 5A RT protein."; RL Virology 230:217-227(1997). RN [17] RP INTERACTION WITH HCV NON-STRUCTURAL PROTEIN 5A (MICROBIAL INFECTION). RX PubMed=9710605; DOI=10.1128/mcb.18.9.5208; RA Gale M.J. Jr., Blakely C.M., Kwieciszewski B., Tan S.-L., Dossett M., RA Tang N.M., Korth M.J., Polyak S.J., Gretch D.R., Katze M.G.; RT "Control of PKR protein kinase by hepatitis C virus nonstructural 5A RT protein: molecular mechanisms of kinase regulation."; RL Mol. Cell. Biol. 18:5208-5218(1998). RN [18] RP INTERACTION WITH INFLUENZA A NS1 PROTEIN. RX PubMed=9781815; DOI=10.1089/jir.1998.18.757; RA Tan S.L., Katze M.G.; RT "Biochemical and genetic evidence for complex formation between the RT influenza A virus NS1 protein and the interferon-induced PKR protein RT kinase."; RL J. Interferon Cytokine Res. 18:757-766(1998). RN [19] RP INTERACTION WITH HCV ENVELOPE GLYCOPROTEIN E2 (MICROBIAL INFECTION). RX PubMed=10390359; DOI=10.1126/science.285.5424.107; RA Taylor D.R., Shi S.T., Romano P.R., Barber G.N., Lai M.M.C.; RT "Inhibition of the interferon-inducible protein kinase PKR by HCV E2 RT protein."; RL Science 285:107-110(1999). RN [20] RP FUNCTION, AND INTERACTION WITH IKBKB. RX PubMed=10848580; DOI=10.1128/mcb.20.13.4532-4542.2000; RA Bonnet M.C., Weil R., Dam E., Hovanessian A.G., Meurs E.F.; RT "PKR stimulates NF-kappaB irrespective of its kinase function by RT interacting with the IkappaB kinase complex."; RL Mol. Cell. Biol. 20:4532-4542(2000). RN [21] RP INTERACTION WITH TARBP2. RX PubMed=11438532; DOI=10.1074/jbc.m103584200; RA Daher A., Longuet M., Dorin D., Bois F., Segeral E., Bannwarth S., RA Battisti P.-L., Purcell D.F., Benarous R., Vaquero C., Meurs E.F., RA Gatignol A.; RT "Two dimerization domains in the trans-activation response RNA-binding RT protein (TRBP) individually reverse the protein kinase R inhibition of HIV- RT 1 long terminal repeat expression."; RL J. Biol. Chem. 276:33899-33905(2001). RN [22] RP PHOSPHORYLATION AT SER-83; THR-88; THR-89; THR-90; SER-242; THR-255 AND RP THR-258, MUTAGENESIS OF SER-83; THR-88; THR-89; THR-90; SER-242; THR-255; RP THR-258 AND LYS-296, AND INHIBITION BY HCV E2 ENVELOPE PROTEIN. RX PubMed=11152499; DOI=10.1128/jvi.75.3.1265-1273.2001; RA Taylor D.R., Tian B., Romano P.R., Hinnebusch A.G., Lai M.M.C., RA Mathews M.B.; RT "Hepatitis C virus envelope protein E2 does not inhibit PKR by simple RT competition with autophosphorylation sites in the RNA-binding domain."; RL J. Virol. 75:1265-1273(2001). RN [23] RP MUTAGENESIS OF LYS-60; ALA-67; THR-446 AND THR-451, AND PHOSPHORYLATION AT RP THR-446 AND THR-451. RX PubMed=11337501; DOI=10.1074/jbc.m102108200; RA Zhang F., Romano P.R., Nagamura-Inoue T., Tian B., Dever T.E., RA Mathews M.B., Ozato K., Hinnebusch A.G.; RT "Binding of double-stranded RNA to protein kinase PKR is required for RT dimerization and promotes critical autophosphorylation events in the RT activation loop."; RL J. Biol. Chem. 276:24946-24958(2001). RN [24] RP INTERACTION WITH HHV-8 PROTEIN VIRF2 (MICROBIAL INFECTION). RX PubMed=11160738; DOI=10.1128/jvi.75.5.2345-2352.2001; RA Burysek L., Pitha P.M.; RT "Latently expressed human herpesvirus 8-encoded interferon regulatory RT factor 2 inhibits double-stranded RNA-activated protein kinase."; RL J. Virol. 75:2345-2352(2001). RN [25] RP FUNCTION, AND INTERACTION WITH HHV-1 US11 (MICROBIAL INFECTION). RX PubMed=11836380; DOI=10.1128/jvi.76.5.2029-2035.2002; RA Cassady K.A., Gross M.; RT "The herpes simplex virus type 1 U(S)11 protein interacts with protein RT kinase R in infected cells and requires a 30-amino-acid sequence adjacent RT to a kinase substrate domain."; RL J. Virol. 76:2029-2035(2002). RN [26] RP INTERACTION WITH NPM1, AND ACTIVITY REGULATION. RX PubMed=12882984; DOI=10.1074/jbc.m301392200; RA Pang Q., Christianson T.A., Koretsky T., Carlson H., David L., Keeble W., RA Faulkner G.R., Speckhart A., Bagby G.C.; RT "Nucleophosmin interacts with and inhibits the catalytic function of RT eukaryotic initiation factor 2 kinase PKR."; RL J. Biol. Chem. 278:41709-41717(2003). RN [27] RP FUNCTION, AND INTERACTION WITH MAP2K6. RX PubMed=15229216; DOI=10.1074/jbc.m406554200; RA Silva A.M., Whitmore M., Xu Z., Jiang Z., Li X., Williams B.R.; RT "Protein kinase R (PKR) interacts with and activates mitogen-activated RT protein kinase kinase 6 (MKK6) in response to double-stranded RNA RT stimulation."; RL J. Biol. Chem. 279:37670-37676(2004). RN [28] RP IDENTIFICATION IN A COMPLEX WITH FANCA; FANCC; FANCG AND HSP70. RX PubMed=15299030; DOI=10.1074/jbc.m403884200; RA Zhang X., Li J., Sejas D.P., Rathbun K.R., Bagby G.C., Pang Q.; RT "The Fanconi anemia proteins functionally interact with the protein kinase RT regulated by RNA (PKR)."; RL J. Biol. Chem. 279:43910-43919(2004). RN [29] RP FUNCTION, INTERACTION WITH TRAF2; TRAF5 AND TRAF6, AND SUBCELLULAR RP LOCATION. RX PubMed=15121867; DOI=10.1128/mcb.24.10.4502-4512.2004; RA Gil J., Garcia M.A., Gomez-Puertas P., Guerra S., Rullas J., Nakano H., RA Alcami J., Esteban M.; RT "TRAF family proteins link PKR with NF-kappa B activation."; RL Mol. Cell. Biol. 24:4502-4512(2004). RN [30] RP INHIBITION BY VACCINIA VIRUS PROTEIN E3 (MICROBIAL INFECTION). RX PubMed=15207627; DOI=10.1016/j.virol.2004.03.012; RA Langland J.O., Jacobs B.L.; RT "Inhibition of PKR by vaccinia virus: role of the N- and C-terminal domains RT of E3L."; RL Virology 324:419-429(2004). RN [31] RP REVIEW. RX PubMed=17158706; DOI=10.1128/mmbr.00027-06; RA Garcia M.A., Gil J., Ventoso I., Guerra S., Domingo E., Rivas C., RA Esteban M.; RT "Impact of protein kinase PKR in cell biology: from antiviral to RT antiproliferative action."; RL Microbiol. Mol. Biol. Rev. 70:1032-1060(2006). RN [32] RP INTERACTION WITH HCMV TRS1 (MICROBIAL INFECTION). RX PubMed=16987971; DOI=10.1128/jvi.00957-06; RA Hakki M., Marshall E.E., De Niro K.L., Geballe A.P.; RT "Binding and nuclear relocalization of protein kinase R by human RT cytomegalovirus TRS1."; RL J. Virol. 80:11817-11826(2006). RN [33] RP PHOSPHORYLATION AT TYR-101; TYR-162 AND TYR-293. RX PubMed=16373505; DOI=10.1073/pnas.0508207103; RA Su Q., Wang S., Baltzis D., Qu L.K., Wong A.H., Koromilas A.E.; RT "Tyrosine phosphorylation acts as a molecular switch to full-scale RT activation of the eIF2alpha RNA-dependent protein kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 103:63-68(2006). RN [34] RP INTERACTION WITH HCV NON-STRUCTURAL PROTEIN 5A (MICROBIAL INFECTION). RX PubMed=16951545; RA Liang Y., Kang C.B., Yoon H.S.; RT "Molecular and structural characterization of the domain 2 of hepatitis C RT virus non-structural protein 5A."; RL Mol. Cells 22:13-20(2006). RN [35] RP INTERACTION WITH HCV NON-STRUCTURAL PROTEIN 5A (MICROBIAL INFECTION). RX PubMed=17451199; DOI=10.3748/wjg.v13.i8.1195; RA Veillon P., Payan C., Le Guillou-Guillemette H., Gaudy C., Lunel F.; RT "Quasispecies evolution in NS5A region of hepatitis C virus genotype 1b RT during interferon or combined interferon-ribavirin therapy."; RL World J. Gastroenterol. 13:1195-1203(2007). RN [36] RP INTERACTION WITH HCV MATURE CORE PROTEIN (MICROBIAL INFECTION). RX PubMed=17267064; DOI=10.1016/j.virusres.2006.12.010; RA Yan X.B., Battaglia S., Boucreux D., Chen Z., Brechot C., Pavio N.; RT "Mapping of the interacting domains of hepatitis C virus core protein and RT the double-stranded RNA-activated protein kinase PKR."; RL Virus Res. 125:79-87(2007). RN [37] RP INTERACTION WITH ADAR. RX PubMed=17079286; DOI=10.1128/jvi.01527-06; RA Nie Y., Hammond G.L., Yang J.H.; RT "Double-stranded RNA deaminase ADAR1 increases host susceptibility to virus RT infection."; RL J. Virol. 81:917-923(2007). RN [38] RP REVIEW ON ACTIVITY REGULATION. RX PubMed=17196820; DOI=10.1016/j.tibs.2006.12.003; RA Cole J.L.; RT "Activation of PKR: an open and shut case?"; RL Trends Biochem. Sci. 32:57-62(2007). RN [39] RP FUNCTION, INTERACTION WITH NCK1, AND ACTIVITY REGULATION. RX PubMed=18835251; DOI=10.1016/j.bbrc.2008.09.112; RA Cardin E., Larose L.; RT "Nck-1 interacts with PKR and modulates its activation by dsRNA."; RL Biochem. Biophys. Res. Commun. 377:231-235(2008). RN [40] RP INTERACTION WITH DUS2L, AND ACTIVITY REGULATION. RX PubMed=18096616; DOI=10.1093/nar/gkm1129; RA Mittelstadt M., Frump A., Khuu T., Fowlkes V., Handy I., Patel C.V., RA Patel R.C.; RT "Interaction of human tRNA-dihydrouridine synthase-2 with interferon- RT induced protein kinase PKR."; RL Nucleic Acids Res. 36:998-1008(2008). RN [41] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83 AND SER-456, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [42] RP MUTAGENESIS OF ASP-486, AND INTERACTION WITH VACCINIA VIRUS PROTEIN K3 RP (MICROBIAL INFECTION). RX PubMed=18971339; DOI=10.1073/pnas.0805524105; RA Seo E.J., Liu F., Kawagishi-Kobayashi M., Ung T.L., Cao C., Dar A.C., RA Sicheri F., Dever T.E.; RT "Protein kinase PKR mutants resistant to the poxvirus pseudosubstrate K3L RT protein."; RL Proc. Natl. Acad. Sci. U.S.A. 105:16894-16899(2008). RN [43] RP FUNCTION. RX PubMed=19507191; DOI=10.1002/jcp.21848; RA Blalock W.L., Grimaldi C., Fala F., Follo M., Horn S., Basecke J., RA Martinelli G., Cocco L., Martelli A.M.; RT "PKR activity is required for acute leukemic cell maintenance and growth: a RT role for PKR-mediated phosphatase activity to regulate GSK-3 RT phosphorylation."; RL J. Cell. Physiol. 221:232-241(2009). RN [44] RP FUNCTION, AND INTERACTION WITH DHX9. RX PubMed=19229320; DOI=10.1371/journal.ppat.1000311; RA Sadler A.J., Latchoumanin O., Hawkes D., Mak J., Williams B.R.; RT "An antiviral response directed by PKR phosphorylation of the RNA helicase RT A."; RL PLoS Pathog. 5:E1000311-E1000311(2009). RN [45] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [46] RP FUNCTION IN HCV RESTRICTION. RX PubMed=19189853; DOI=10.1016/j.virusres.2009.01.007; RA Kang J.I., Kwon S.N., Park S.H., Kim Y.K., Choi S.Y., Kim J.P., Ahn B.Y.; RT "PKR protein kinase is activated by hepatitis C virus and inhibits viral RT replication through translational control."; RL Virus Res. 142:51-56(2009). RN [47] RP FUNCTION. RX PubMed=20171114; DOI=10.1016/j.cyto.2010.01.008; RA Lin S.S., Lee D.C., Law A.H., Fang J.W., Chua D.T., Lau A.S.; RT "A role for protein kinase PKR in the mediation of Epstein-Barr virus RT latent membrane protein-1-induced IL-6 and IL-10 expression."; RL Cytokine 50:210-219(2010). RN [48] RP FUNCTION AS CDK1 KINASE UPON DNA DAMAGE, AND FUNCTION AS TYROSINE-PROTEIN RP KINASE. RX PubMed=20395957; DOI=10.1038/embor.2010.45; RA Yoon C.-H., Miah M.A., Kim K.P., Bae Y.-S.; RT "New Cdc2 Tyr 4 phosphorylation by dsRNA-activated protein kinase triggers RT Cdc2 polyubiquitination and G2 arrest under genotoxic stresses."; RL EMBO Rep. 11:393-399(2010). RN [49] RP FUNCTION. RX PubMed=21123651; DOI=10.1101/gad.1965010; RA Harashima A., Guettouche T., Barber G.N.; RT "Phosphorylation of the NFAR proteins by the dsRNA-dependent protein kinase RT PKR constitutes a novel mechanism of translational regulation and cellular RT defense."; RL Genes Dev. 24:2640-2653(2010). RN [50] RP INTERACTION WITH HRSV NUCLEOPROTEIN (MICROBIAL INFECTION). RX PubMed=20519500; DOI=10.1074/jbc.m109.077321; RA Groskreutz D.J., Babor E.C., Monick M.M., Varga S.M., Hunninghake G.W.; RT "Respiratory syncytial virus limits alpha subunit of eukaryotic translation RT initiation factor 2 (eIF2alpha) phosphorylation to maintain translation and RT viral replication."; RL J. Biol. Chem. 285:24023-24031(2010). RN [51] RP FUNCTION IN HCV RESTRICTION. RX PubMed=19840259; DOI=10.1111/j.1478-3231.2009.02144.x; RA Chang J.H., Kato N., Muroyama R., Taniguchi H., Guleng B., Dharel N., RA Shao R.X., Tateishi K., Jazag A., Kawabe T., Omata M.; RT "Double-stranded RNA-activated protein kinase inhibits hepatitis C virus RT replication but may be not essential in interferon treatment."; RL Liver Int. 30:311-318(2010). RN [52] RP FUNCTION, AND PHOSPHORYLATION AT THR-451. RX PubMed=20685959; DOI=10.1091/mbc.e10-06-0481; RA Yang X., Nath A., Opperman M.J., Chan C.; RT "The double-stranded RNA-dependent protein kinase differentially regulates RT insulin receptor substrates 1 and 2 in HepG2 cells."; RL Mol. Biol. Cell 21:3449-3458(2010). RN [53] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [54] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [55] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND PHOSPHORYLATION. RX PubMed=21029237; DOI=10.1111/j.1750-3639.2010.00437.x; RA Bose A., Mouton-Liger F., Paquet C., Mazot P., Vigny M., Gray F., Hugon J.; RT "Modulation of tau phosphorylation by the kinase PKR: implications in RT Alzheimer's disease."; RL Brain Pathol. 21:189-200(2011). RN [56] RP REVIEW. RX PubMed=21924887; DOI=10.1016/j.coi.2011.08.009; RA Pfaller C.K., Li Z., George C.X., Samuel C.E.; RT "Protein kinase PKR and RNA adenosine deaminase ADAR1: new roles for old RT players as modulators of the interferon response."; RL Curr. Opin. Immunol. 23:573-582(2011). RN [57] RP REVIEW. RX PubMed=21166592; DOI=10.1089/jir.2010.0099; RA Pindel A., Sadler A.; RT "The role of protein kinase R in the interferon response."; RL J. Interferon Cytokine Res. 31:59-70(2011). RN [58] RP FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY, AND RP PHOSPHORYLATION. RX PubMed=21072047; DOI=10.1038/leu.2010.264; RA Blalock W.L., Bavelloni A., Piazzi M., Tagliavini F., Faenza I., RA Martelli A.M., Follo M.Y., Cocco L.; RT "Multiple forms of PKR present in the nuclei of acute leukemia cells RT represent an active kinase that is responsive to stress."; RL Leukemia 25:236-245(2011). RN [59] RP FUNCTION IN HBV RESTRICTION. RX PubMed=21710204; DOI=10.1007/s10059-011-1059-6; RA Park I.H., Baek K.W., Cho E.Y., Ahn B.Y.; RT "PKR-dependent mechanisms of interferon-? for inhibiting hepatitis B virus RT replication."; RL Mol. Cells 32:167-172(2011). RN [60] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=22214662; DOI=10.4161/cc.11.2.18999; RA Bennett R.L., Pan Y., Christian J., Hui T., May W.S. Jr.; RT "The RAX/PACT-PKR stress response pathway promotes p53 sumoylation and RT activation, leading to G(1) arrest."; RL Cell Cycle 11:407-417(2012). RN [61] RP REVIEW. RX PubMed=22633454; DOI=10.1016/j.immuni.2012.05.010; RA Lacy-Hulbert A., Stuart L.M.; RT "Penetration resistance: PKR's other talent."; RL Immunity 36:695-696(2012). RN [62] RP FUNCTION. RX PubMed=22948139; DOI=10.1074/jbc.m112.390039; RA McAllister C.S., Taghavi N., Samuel C.E.; RT "Protein kinase PKR amplification of interferon beta induction occurs RT through initiation factor eIF-2alpha-mediated translational control."; RL J. Biol. Chem. 287:36384-36392(2012). RN [63] RP FUNCTION, AND INTERACTION WITH STAT3. RX PubMed=23084476; DOI=10.1016/j.molcel.2012.09.013; RA Shen S., Niso-Santano M., Adjemian S., Takehara T., Malik S.A., Minoux H., RA Souquere S., Marino G., Lachkar S., Senovilla L., Galluzzi L., Kepp O., RA Pierron G., Maiuri M.C., Hikita H., Kroemer R., Kroemer G.; RT "Cytoplasmic STAT3 represses autophagy by inhibiting PKR activity."; RL Mol. Cell 48:667-680(2012). RN [64] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [65] RP FUNCTION, INTERACTION WITH NLRP1; NLRP3; NLRC4 AND AIM2, AND RP AUTOPHOSPHORYLATION. RX PubMed=22801494; DOI=10.1038/nature11290; RA Lu B., Nakamura T., Inouye K., Li J., Tang Y., Lundbaeck P., RA Valdes-Ferrer S.I., Olofsson P.S., Kalb T., Roth J., Zou Y., RA Erlandsson-Harris H., Yang H., Ting J.P., Wang H., Andersson U., RA Antoine D.J., Chavan S.S., Hotamisligil G.S., Tracey K.J.; RT "Novel role of PKR in inflammasome activation and HMGB1 release."; RL Nature 488:670-674(2012). RN [66] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [67] RP REVIEW. RX PubMed=23092889; DOI=10.1126/scisignal.2003511; RA Kang R., Tang D.; RT "PKR-dependent inflammatory signals."; RL Sci. Signal. 5:PE47-PE47(2012). RN [68] RP FUNCTION. RX PubMed=22381929; DOI=10.1016/j.virol.2012.01.029; RA Taghavi N., Samuel C.E.; RT "Protein kinase PKR catalytic activity is required for the PKR-dependent RT activation of mitogen-activated protein kinases and amplification of RT interferon beta induction following virus infection."; RL Virology 427:208-216(2012). RN [69] RP REVIEW. RX PubMed=23202496; DOI=10.3390/v4112598; RA Dabo S., Meurs E.F.; RT "dsRNA-dependent protein kinase PKR and its role in stress, signaling and RT HCV infection."; RL Viruses 4:2598-2635(2012). RN [70] RP TISSUE SPECIFICITY. RX PubMed=23403623; DOI=10.1182/blood-2012-09-456400; RA Liu X., Bennett R.L., Cheng X., Byrne M., Reinhard M.K., May W.S. Jr.; RT "PKR regulates proliferation, differentiation and survival of murine RT hematopoietic stem/progenitor cells."; RL Blood 121:3364-3374(2013). RN [71] RP REVIEW. RX PubMed=23354059; DOI=10.1007/s00018-012-1252-6; RA Donnelly N., Gorman A.M., Gupta S., Samali A.; RT "The eIF2alpha kinases: their structures and functions."; RL Cell. Mol. Life Sci. 70:3493-3511(2013). RN [72] RP FUNCTION, ISGYLATION AT LYS-69 AND LYS-159, AND ACTIVITY REGULATION. RX PubMed=23229543; DOI=10.1074/jbc.m112.401851; RA Okumura F., Okumura A.J., Uematsu K., Hatakeyama S., Zhang D.E., Kamura T.; RT "Activation of double-stranded RNA-activated protein kinase (PKR) by RT interferon-stimulated gene 15 (ISG15) modification down-regulates protein RT translation."; RL J. Biol. Chem. 288:2839-2847(2013). RN [73] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-542, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [74] RP INTERACTION WITH TOSCANA VIRUS PROTEIN NSS (MICROBIAL INFECTION), AND RP ACTIVITY REGULATION. RX PubMed=23325696; DOI=10.1128/jvi.02506-12; RA Kalveram B., Ikegami T.; RT "Toscana virus NSs protein promoftes degradation of double-stranded RNA- RT dependent protein kinase."; RL J. Virol. 87:3710-3718(2013). RN [75] RP FUNCTION IN MV RESTRICTION. RX PubMed=23115276; DOI=10.1128/jvi.02270-12; RA Okonski K.M., Samuel C.E.; RT "Stress granule formation induced by measles virus is protein kinase PKR RT dependent and impaired by RNA adenosine deaminase ADAR1."; RL J. Virol. 87:756-766(2013). RN [76] RP FUNCTION. RX PubMed=23372823; DOI=10.1371/journal.pone.0055108; RA Li Y., Xie J., Wu S., Xia J., Zhang P., Liu C., Zhang P., Huang X.; RT "Protein kinase regulated by dsRNA downregulates the interferon production RT in dengue virus- and dsrna-stimulated human lung epithelial cells."; RL PLoS ONE 8:E55108-E55108(2013). RN [77] RP FUNCTION IN HCV RESTRICTION. RX PubMed=23399035; DOI=10.1016/j.virol.2013.01.015; RA Zhang L., Alter H.J., Wang H., Jia S., Wang E., Marincola F.M., Shih J.W., RA Wang R.Y.; RT "The modulation of hepatitis C virus 1a replication by PKR is dependent on RT NF-kB mediated interferon beta response in Huh7.5.1 cells."; RL Virology 438:28-36(2013). RN [78] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [79] RP INTERACTION WITH VACCINIA VIRUS PROTEIN E3 (MICROBIAL INFECTION). RX PubMed=25740987; DOI=10.1128/jvi.03288-14; RA Dueck K.J., Hu Y.S., Chen P., Deschambault Y., Lee J., Varga J., Cao J.; RT "Mutational analysis of vaccinia virus E3 protein: the biological functions RT do not correlate with its biochemical capacity to bind double-stranded RT RNA."; RL J. Virol. 89:5382-5394(2015). RN [80] RP MUTAGENESIS OF PHE-489; THR-496; ILE-502; ILE-506; LYS-510 AND GLN-516, AND RP INTERACTION WITH HCMV TRS1 (MICROBIAL INFECTION). RX PubMed=27780231; DOI=10.1371/journal.ppat.1005966; RA Carpentier K.S., Esparo N.M., Child S.J., Geballe A.P.; RT "A Single Amino Acid Dictates Protein Kinase R Susceptibility to Unrelated RT Viral Antagonists."; RL PLoS Pathog. 12:e1005966-e1005966(2016). RN [81] RP INTERACTION WITH HUMAN HERPES VIRUS 8 PROTEIN KTA/ORF57 (MICROBIAL RP INFECTION). RX PubMed=29084250; DOI=10.1371/journal.ppat.1006677; RA Sharma N.R., Majerciak V., Kruhlak M.J., Zheng Z.M.; RT "KSHV inhibits stress granule formation by viral ORF57 blocking PKR RT activation."; RL PLoS Pathog. 13:e1006677-e1006677(2017). RN [82] {ECO:0007744|PDB:1QU6} RP STRUCTURE BY NMR OF 1-170, AND DOMAIN. RX PubMed=9736623; DOI=10.1093/emboj/17.18.5458; RA Nanduri S., Carpick B.W., Yang Y., Williams B.R.G., Qin J.; RT "Structure of the double-stranded RNA-binding domain of the protein kinase RT PKR reveals the molecular basis of its dsRNA-mediated activation."; RL EMBO J. 17:5458-5465(1998). RN [83] {ECO:0007744|PDB:2A19, ECO:0007744|PDB:2A1A} RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 258-550 IN COMPLEX WITH RP EIF2S1/EIF-2ALPHA, PHOSPHORYLATION AT THR-446, DOMAIN, SUBUNIT, COFACTOR, RP AND INTERACTION WITH EIF2S1/EIF-2ALPHA. RX PubMed=16179258; DOI=10.1016/j.cell.2005.06.044; RA Dar A.C., Dever T.E., Sicheri F.; RT "Higher-order substrate recognition of eIF2alpha by the RNA-dependent RT protein kinase PKR."; RL Cell 122:887-900(2005). RN [84] {ECO:0007744|PDB:6D3K, ECO:0007744|PDB:6D3L} RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 229-551, AND SUBUNIT. RX PubMed=31246429; DOI=10.1021/acs.biochem.9b00161; RA Mayo C.B., Erlandsen H., Mouser D.J., Feinstein A.G., Robinson V.L., RA May E.R., Cole J.L.; RT "Structural Basis of Protein Kinase R Autophosphorylation."; RL Biochemistry 58:2967-2977(2019). RN [85] RP INVOLVEMENT IN LEUDEN, FUNCTION, VARIANTS LEUDEN LEU-11; SER-32; PHE-97; RP SER-109; VAL-109; PHE-133; SER-325 AND CYS-461, CHARACTERIZATION OF RP VARIANTS LEUDEN LEU-11; PHE-133 AND CYS-461, AND VARIANT GLN-114. RX PubMed=32197074; DOI=10.1016/j.ajhg.2020.02.016; RG Undiagnosed Diseases Network; RA Mao D., Reuter C.M., Ruzhnikov M.R.Z., Beck A.E., Farrow E.G., Emrick L.T., RA Rosenfeld J.A., Mackenzie K.M., Robak L., Wheeler M.T., Burrage L.C., RA Jain M., Liu P., Calame D., Kuery S., Sillesen M., Schmitz-Abe K., RA Tonduti D., Spaccini L., Iascone M., Genetti C.A., Koenig M.K., Graf M., RA Tran A., Alejandro M., Lee B.H., Thiffault I., Agrawal P.B., RA Bernstein J.A., Bellen H.J., Chao H.T.; RT "De novo EIF2AK1 and EIF2AK2 variants are associated with developmental RT delay, leukoencephalopathy, and neurologic decompensation."; RL Am. J. Hum. Genet. 106:570-583(2020). RN [86] RP VARIANTS [LARGE SCALE ANALYSIS] GLU-428; VAL-439 AND VAL-506. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). RN [87] RP VARIANTS DYT33 THR-32; ARG-130 AND ALA-138, CHARACTERIZATION OF VARIANTS RP DYT33 THR-32 AND ARG-130, AND INVOLVEMENT IN DYT33. RX PubMed=33236446; DOI=10.1002/ana.25973; RA Kuipers D.J.S., Mandemakers W., Lu C.S., Olgiati S., Breedveld G.J., RA Fevga C., Tadic V., Carecchio M., Osterman B., Sagi-Dain L., Wu-Chou Y.H., RA Chen C.C., Chang H.C., Wu S.L., Yeh T.H., Weng Y.H., Elia A.E., RA Panteghini C., Marotta N., Pauly M.G., Kuehn A.A., Volkmann J., Lace B., RA Meijer I.A., Kandaswamy K., Quadri M., Garavaglia B., Lohmann K., Bauer P., RA Mencacci N.E., Lubbe S.J., Klein C., Bertoli-Avella A.M., Bonifati V.; RT "EIF2AK2 Missense Variants Associated with Early Onset Generalized RT Dystonia."; RL Ann. Neurol. 89:485-497(2021). RN [88] RP VARIANT DYT33 ARG-130, AND INVOLVEMENT IN DYT33. RX PubMed=33866603; DOI=10.1002/ana.26081; RA Musacchio T., Zech M., Reich M.M., Winkelmann J., Volkmann J.; RT "A Recurrent EIF2AK2 Missense Variant Causes Autosomal-Dominant Isolated RT Dystonia."; RL Ann. Neurol. 89:1257-1258(2021). RN [89] RP VARIANT DYT33 ARG-130. RX PubMed=35146068; DOI=10.1002/mdc3.13371; RA Magrinelli F., Moualek D., Tazir M., Pacha L.A., Verghese A., Bhatia K.P., RA Maroofian R., Houlden H.; RT "Heterozygous EIF2AK2 Variant Causes Adolescence-Onset Generalized Dystonia RT Partially Responsive to DBS."; RL Mov. Disord. Clin. Pract. 9:268-271(2022). CC -!- FUNCTION: IFN-induced dsRNA-dependent serine/threonine-protein kinase CC that phosphorylates the alpha subunit of eukaryotic translation CC initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the CC innate immune response to viral infection (PubMed:18835251, CC PubMed:19507191, PubMed:19189853, PubMed:21123651, PubMed:21072047, CC PubMed:22948139, PubMed:23229543, PubMed:22381929). Inhibits viral CC replication via the integrated stress response (ISR): EIF2S1/eIF-2- CC alpha phosphorylation in response to viral infection converts CC EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, resulting CC to a shutdown of cellular and viral protein synthesis, while CC concomitantly initiating the preferential translation of ISR-specific CC mRNAs, such as the transcriptional activator ATF4 (PubMed:19189853, CC PubMed:21123651, PubMed:22948139, PubMed:23229543). Exerts its CC antiviral activity on a wide range of DNA and RNA viruses including CC hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) CC and herpes simplex virus 1 (HHV-1) (PubMed:11836380, PubMed:19189853, CC PubMed:20171114, PubMed:19840259, PubMed:21710204, PubMed:23115276, CC PubMed:23399035). Also involved in the regulation of signal CC transduction, apoptosis, cell proliferation and differentiation: CC phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, CC ILF3, IRS1 and the HHV-1 viral protein US11 (PubMed:11836380, CC PubMed:22214662, PubMed:19229320). In addition to serine/threonine- CC protein kinase activity, also has tyrosine-protein kinase activity and CC phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its CC ubiquitination and proteasomal degradation (PubMed:20395957). Either as CC an adapter protein and/or via its kinase activity, can regulate various CC signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling CC pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) CC involved in the expression of genes encoding pro-inflammatory cytokines CC and IFNs (PubMed:22948139, PubMed:23084476, PubMed:23372823). Activates CC the NF-kappa-B pathway via interaction with IKBKB and TRAF family of CC proteins and activates the p38 MAP kinase pathway via interaction with CC MAP2K6 (PubMed:10848580, PubMed:15121867, PubMed:15229216). Can act as CC both a positive and negative regulator of the insulin signaling pathway CC (ISP) (PubMed:20685959). Negatively regulates ISP by inducing the CC inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at CC 'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5A CC which activates FOXO1, which in turn up-regulates the expression of CC insulin receptor substrate 2 (IRS2) (PubMed:20685959). Can regulate CC NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 CC and NLRC4 inflammasomes (PubMed:22801494). Plays a role in the CC regulation of the cytoskeleton by binding to gelsolin (GSN), CC sequestering the protein in an inactive conformation away from actin CC (By similarity). {ECO:0000250|UniProtKB:Q03963, CC ECO:0000269|PubMed:10848580, ECO:0000269|PubMed:11836380, CC ECO:0000269|PubMed:15121867, ECO:0000269|PubMed:15229216, CC ECO:0000269|PubMed:18835251, ECO:0000269|PubMed:19189853, CC ECO:0000269|PubMed:19229320, ECO:0000269|PubMed:19507191, CC ECO:0000269|PubMed:19840259, ECO:0000269|PubMed:20171114, CC ECO:0000269|PubMed:20395957, ECO:0000269|PubMed:20685959, CC ECO:0000269|PubMed:21072047, ECO:0000269|PubMed:21123651, CC ECO:0000269|PubMed:21710204, ECO:0000269|PubMed:22214662, CC ECO:0000269|PubMed:22381929, ECO:0000269|PubMed:22801494, CC ECO:0000269|PubMed:22948139, ECO:0000269|PubMed:23084476, CC ECO:0000269|PubMed:23115276, ECO:0000269|PubMed:23229543, CC ECO:0000269|PubMed:23372823, ECO:0000269|PubMed:23399035, CC ECO:0000269|PubMed:32197074}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; CC EC=2.7.11.1; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10027}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:16179258, ECO:0000303|PubMed:31246429}; CC -!- ACTIVITY REGULATION: Initially produced in an inactive form and is CC activated by binding to viral dsRNA, which causes dimerization and CC autophosphorylation in the activation loop and stimulation of function. CC ISGylation can activate it in the absence of viral infection. Can also CC be activated by heparin, pro-inflammatory stimuli, growth factors, CC cytokines, oxidative stress and the cellular protein PRKRA. Activity is CC markedly stimulated by manganese ions. Activation is blocked by the CC viral components HIV-1 Tat protein and large amounts of HIV-1 trans- CC activation response (TAR) RNA element as well as by the cellular CC proteins TARBP2, DUS2L, NPM1, NCK1 and ADAR. Down-regulated by Toscana CC virus (TOS) and Rift valley fever virus (RVFV) NSS which promote its CC proteasomal degradation. Inhibited by vaccinia virus protein E3, CC probably via dsRNA sequestering. {ECO:0000269|PubMed:12882984, CC ECO:0000269|PubMed:18096616, ECO:0000269|PubMed:18835251, CC ECO:0000269|PubMed:23229543, ECO:0000269|PubMed:23325696}. CC -!- SUBUNIT: Homodimer (PubMed:16179258, PubMed:31246429). Interacts with CC STRBP (By similarity). Interacts with DNAJC3. Forms a complex with CC FANCA, FANCC, FANCG and HSP70. Interacts with ADAR/ADAR1. Interacts CC with IRS1 (By similarity). The inactive form interacts with NCK1 and CC GSN. Interacts (via the kinase catalytic domain) with STAT3 (via SH2 CC domain), TRAF2 (C-terminus), TRAF5 (C-terminus) and TRAF6 (C-terminus). CC Interacts with MAP2K6, IKBKB/IKKB, NPM1, TARBP2, NLRP1, NLRP3, NLRC4 CC and AIM2. Interacts (via DRBM 1 domain) with DUS2L (via DRBM domain). CC Interacts with DHX9 (via N-terminus) and this interaction is dependent CC upon activation of the kinase. Interacts with EIF2S1/EIF-2ALPHA; this CC interaction induces a conformational change in EIF2S1 and its CC phosphorylation by EIF2AK2 (PubMed:16179258). CC {ECO:0000250|UniProtKB:Q03963, ECO:0000269|PubMed:10390359, CC ECO:0000269|PubMed:10848580, ECO:0000269|PubMed:11438532, CC ECO:0000269|PubMed:12882984, ECO:0000269|PubMed:15121867, CC ECO:0000269|PubMed:15229216, ECO:0000269|PubMed:15299030, CC ECO:0000269|PubMed:16179258, ECO:0000269|PubMed:17079286, CC ECO:0000269|PubMed:18096616, ECO:0000269|PubMed:18835251, CC ECO:0000269|PubMed:19229320, ECO:0000269|PubMed:22801494, CC ECO:0000269|PubMed:23084476, ECO:0000269|PubMed:25740987, CC ECO:0000269|PubMed:31246429, ECO:0000269|PubMed:8576172, CC ECO:0000269|PubMed:9079663, ECO:0000269|PubMed:9143277, CC ECO:0000269|PubMed:9781815}. CC -!- SUBUNIT: (Microbial infection) Interacts with human cytomegalovirus CC (HCMV) TRS1; this interaction retains EIF2AK2 to the nucleus and CC prevents its activation. {ECO:0000269|PubMed:16987971, CC ECO:0000269|PubMed:27780231}. CC -!- SUBUNIT: (Microbial infection) Interacts with vaccinia virus protein K3 CC (K3L); this interaction inhibits EIF2AK2. CC {ECO:0000269|PubMed:18971339}. CC -!- SUBUNIT: (Microbial infection) Interacts with human herpes simplex CC virus 1 (HHV-1) protein US11 in an RNA-dependent manner. CC {ECO:0000269|PubMed:11836380}. CC -!- SUBUNIT: (Microbial infection) The inactive form interacts with Toscana CC virus (TOS) NSS. {ECO:0000269|PubMed:23325696}. CC -!- SUBUNIT: (Microbial infection) Interacts with herpes virus 8 protein v- CC IRF2; this interaction inhibits EIF2AK2 activation. CC {ECO:0000269|PubMed:11160738}. CC -!- SUBUNIT: (Microbial infection) Interacts with vaccinia protein E3. CC {ECO:0000269|PubMed:25740987}. CC -!- SUBUNIT: (Microbial infection) Interacts (via N-terminus) with CC Hepatitis C virus (HCV) mature core protein (via N-terminus); this CC interaction induces the autophosphorylation of EIF2AK2. CC {ECO:0000269|PubMed:17267064}. CC -!- SUBUNIT: (Microbial infection) Interacts with Hepatitis C virus (HCV) CC non-structural protein 5A (NS5A); this interaction leads to disruption CC of EIF2AK2 dimerization by NS5A. {ECO:0000269|PubMed:16951545, CC ECO:0000269|PubMed:17451199, ECO:0000269|PubMed:9143277, CC ECO:0000269|PubMed:9710605}. CC -!- SUBUNIT: (Microbial infection) Interacts with Hepatitis C virus (HCV) CC envelope glycoprotein E2; this interaction inhibits EIF2AK2 and blocks CC its inhibitory effect on protein synthesis and cell growth. CC {ECO:0000269|PubMed:9143277}. CC -!- SUBUNIT: (Microbial infection) Interacts with human respiratory CC syncytial virus (HRSV) nucleoprotein; this interaction inhibits EIF2AK2 CC phosphorylation of EIF2S1 and blocks EIF2AK2-mediated translation CC shutoff. {ECO:0000269|PubMed:20519500}. CC -!- SUBUNIT: (Microbial infection) Interacts with human herpesvirus 8 CC protein MTA/ORF57; this interaction inhibits stress granule formation. CC {ECO:0000269|PubMed:29084250}. CC -!- INTERACTION: CC P19525; P78563-4: ADARB1; NbExp=3; IntAct=EBI-640775, EBI-12002366; CC P19525; P06493: CDK1; NbExp=4; IntAct=EBI-640775, EBI-444308; CC P19525; Q7L2E3: DHX30; NbExp=4; IntAct=EBI-640775, EBI-1211456; CC P19525; Q96C10: DHX58; NbExp=2; IntAct=EBI-640775, EBI-744193; CC P19525; Q08211: DHX9; NbExp=2; IntAct=EBI-640775, EBI-352022; CC P19525; Q9UPY3: DICER1; NbExp=2; IntAct=EBI-640775, EBI-395506; CC P19525; Q6P2E9: EDC4; NbExp=2; IntAct=EBI-640775, EBI-1006038; CC P19525; P19525: EIF2AK2; NbExp=2; IntAct=EBI-640775, EBI-640775; CC P19525; P05198: EIF2S1; NbExp=5; IntAct=EBI-640775, EBI-1056162; CC P19525; P56537: EIF6; NbExp=2; IntAct=EBI-640775, EBI-372243; CC P19525; Q8IY81: FTSJ3; NbExp=3; IntAct=EBI-640775, EBI-744088; CC P19525; Q9HCE1: MOV10; NbExp=3; IntAct=EBI-640775, EBI-1055820; CC P19525; Q96P20: NLRP3; NbExp=6; IntAct=EBI-640775, EBI-6253230; CC P19525; P06748: NPM1; NbExp=3; IntAct=EBI-640775, EBI-78579; CC P19525; O75569: PRKRA; NbExp=6; IntAct=EBI-640775, EBI-713955; CC P19525; O75569-1: PRKRA; NbExp=3; IntAct=EBI-640775, EBI-15588172; CC P19525; Q9NUL3: STAU2; NbExp=3; IntAct=EBI-640775, EBI-722938; CC P19525; Q15633: TARBP2; NbExp=2; IntAct=EBI-640775, EBI-978581; CC P19525; Q9H0E2: TOLLIP; NbExp=2; IntAct=EBI-640775, EBI-74615; CC P19525; Q9UL40: ZNF346; NbExp=3; IntAct=EBI-640775, EBI-2462313; CC P19525; Q27968: DNAJC3; Xeno; NbExp=5; IntAct=EBI-640775, EBI-640793; CC P19525; P0DTC9: N; Xeno; NbExp=8; IntAct=EBI-640775, EBI-25475856; CC P19525; P20639: OPG041; Xeno; NbExp=3; IntAct=EBI-640775, EBI-8674942; CC P19525; P04487: US11; Xeno; NbExp=3; IntAct=EBI-640775, EBI-6150681; CC P19525; Q2HR71: vIRF-2; Xeno; NbExp=2; IntAct=EBI-640775, EBI-8876177; CC P19525; PRO_0000278746 [O92972]; Xeno; NbExp=2; IntAct=EBI-640775, EBI-6918883; CC P19525; PRO_0000037570 [P27958]; Xeno; NbExp=4; IntAct=EBI-640775, EBI-6904269; CC P19525; PRO_0000037576 [P27958]; Xeno; NbExp=5; IntAct=EBI-640775, EBI-8753518; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15121867, CC ECO:0000269|PubMed:21029237, ECO:0000269|PubMed:22214662}. Nucleus CC {ECO:0000269|PubMed:21029237, ECO:0000269|PubMed:21072047}. Cytoplasm, CC perinuclear region {ECO:0000269|PubMed:15121867}. Note=Nuclear CC localization is elevated in acute leukemia, myelodysplastic syndrome CC (MDS), melanoma, breast, colon, prostate and lung cancer patient CC samples or cell lines as well as neurocytes from advanced Creutzfeldt- CC Jakob disease patients. {ECO:0000269|PubMed:21072047}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P19525-1; Sequence=Displayed; CC Name=2; CC IsoId=P19525-2; Sequence=VSP_046177; CC -!- TISSUE SPECIFICITY: Highly expressed in thymus, spleen and bone marrow CC compared to non-hematopoietic tissues such as small intestine, liver, CC or kidney tissues. Colocalizes with GSK3B and TAU in the Alzheimer CC disease (AD) brain. Elevated levels seen in breast and colon CC carcinomas, and which correlates with tumor progression and CC invasiveness or risk of progression. {ECO:0000269|PubMed:21029237, CC ECO:0000269|PubMed:23403623}. CC -!- INDUCTION: By type I interferons. {ECO:0000269|PubMed:1695551}. CC -!- DOMAIN: Contains 2 dsRNA-binding domain (DRBM) (PubMed:9736623). The N- CC terminus contains the catalytic domain dimerization. The C-terminus CC binds EIF2S1/EIF2-alpha (PubMed:16179258). CC {ECO:0000269|PubMed:16179258, ECO:0000269|PubMed:9736623}. CC -!- PTM: Autophosphorylated on several Ser, Thr and Tyr residues. CC Autophosphorylation of Thr-451 is dependent on Thr-446 and is CC stimulated by dsRNA binding and dimerization. Autophosphorylation CC apparently leads to the activation of the kinase. Tyrosine CC autophosphorylation is essential for efficient dsRNA-binding, CC dimerization, and kinase activation. {ECO:0000269|PubMed:11152499, CC ECO:0000269|PubMed:11337501, ECO:0000269|PubMed:16179258, CC ECO:0000269|PubMed:16373505, ECO:0000269|PubMed:20685959, CC ECO:0000269|PubMed:21029237, ECO:0000269|PubMed:21072047}. CC -!- DISEASE: Leukoencephalopathy, developmental delay, and episodic CC neurologic regression syndrome (LEUDEN) [MIM:618877]: An autosomal CC dominant disorder characterized by global developmental delay apparent CC in early childhood, cognitive impairment, ataxia, poor or absent speech CC with dysarthria, hypotonia, hypertonia, extrapyramidal signs, tremor, CC and abnormal involuntary movements. Affected individuals also exhibit CC neurological regression in the setting of febrile illness or infection. CC Many patients have seizures. Brain imaging shows diffuse white matter CC abnormalities with poor myelination. {ECO:0000269|PubMed:32197074}. CC Note=The disease may be caused by variants affecting the gene CC represented in this entry. CC -!- DISEASE: Dystonia 33 (DYT33) [MIM:619687]: A form of dystonia, a CC disorder defined by the presence of sustained involuntary muscle CC contraction, often leading to abnormal postures. DYT33 is a slowly CC progressive form characterized by onset of focal or generalized CC dystonia in the first decades of life. Disease manifestations are CC variable. Some patients show ambulation difficulties, dysarthria, or CC dysphagia. Some affected individuals may manifest motor delay, lower CC limb spasticity, and mild developmental delay with intellectual CC disability. DYT33 penetrance is incomplete. Inheritance can be CC autosomal dominant or recessive. {ECO:0000269|PubMed:33236446, CC ECO:0000269|PubMed:33866603, ECO:0000269|PubMed:35146068}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein CC kinase family. GCN2 subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/prkr/"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/41866/EIF2AK2"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M35663; AAA36409.1; -; mRNA. DR EMBL; M85294; AAA18253.1; -; mRNA. DR EMBL; U50648; AAC50768.1; -; Genomic_DNA. DR EMBL; U50634; AAC50768.1; JOINED; Genomic_DNA. DR EMBL; U50635; AAC50768.1; JOINED; Genomic_DNA. DR EMBL; U50636; AAC50768.1; JOINED; Genomic_DNA. DR EMBL; U50637; AAC50768.1; JOINED; Genomic_DNA. DR EMBL; U50638; AAC50768.1; JOINED; Genomic_DNA. DR EMBL; U50639; AAC50768.1; JOINED; Genomic_DNA. DR EMBL; U50640; AAC50768.1; JOINED; Genomic_DNA. DR EMBL; U50641; AAC50768.1; JOINED; Genomic_DNA. DR EMBL; U50642; AAC50768.1; JOINED; Genomic_DNA. DR EMBL; U50643; AAC50768.1; JOINED; Genomic_DNA. DR EMBL; U50644; AAC50768.1; JOINED; Genomic_DNA. DR EMBL; U50645; AAC50768.1; JOINED; Genomic_DNA. DR EMBL; U50646; AAC50768.1; JOINED; Genomic_DNA. DR EMBL; U50647; AAC50768.1; JOINED; Genomic_DNA. DR EMBL; AF167472; AAF13156.1; -; Genomic_DNA. DR EMBL; AF167460; AAF13156.1; JOINED; Genomic_DNA. DR EMBL; AF167462; AAF13156.1; JOINED; Genomic_DNA. DR EMBL; AF167463; AAF13156.1; JOINED; Genomic_DNA. DR EMBL; AF167464; AAF13156.1; JOINED; Genomic_DNA. DR EMBL; AF167465; AAF13156.1; JOINED; Genomic_DNA. DR EMBL; AF167466; AAF13156.1; JOINED; Genomic_DNA. DR EMBL; AF167468; AAF13156.1; JOINED; Genomic_DNA. DR EMBL; AF167470; AAF13156.1; JOINED; Genomic_DNA. DR EMBL; AY302136; AAP57628.1; -; mRNA. DR EMBL; AK290655; BAF83344.1; -; mRNA. DR EMBL; AK313818; BAG36554.1; -; mRNA. DR EMBL; AY228338; AAO38055.1; -; Genomic_DNA. DR EMBL; AC007899; AAY24317.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00407.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00408.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00409.1; -; Genomic_DNA. DR EMBL; BC093676; AAH93676.1; -; mRNA. DR EMBL; BC101475; AAI01476.1; -; mRNA. DR CCDS; CCDS1786.1; -. [P19525-1] DR CCDS; CCDS46259.1; -. [P19525-2] DR PIR; JC5225; JC5225. DR RefSeq; NP_001129123.1; NM_001135651.2. [P19525-1] DR RefSeq; NP_001129124.1; NM_001135652.2. [P19525-2] DR RefSeq; NP_002750.1; NM_002759.3. [P19525-1] DR RefSeq; XP_011531289.1; XM_011532987.2. [P19525-1] DR PDB; 1QU6; NMR; -; A=1-170. DR PDB; 2A19; X-ray; 2.50 A; B/C=258-550. DR PDB; 2A1A; X-ray; 2.80 A; B=258-550. DR PDB; 3UIU; X-ray; 2.90 A; A/B=254-551. DR PDB; 6D3K; X-ray; 2.60 A; A/B/C=229-551. DR PDB; 6D3L; X-ray; 3.10 A; A=229-551. DR PDB; 7OBK; X-ray; 1.80 A; B=541-551. DR PDB; 7OBL; X-ray; 1.80 A; B=541-551. DR PDB; 8BI7; X-ray; 1.40 A; B=541-551. DR PDB; 8I9J; EM; 6.39 A; A=1-170. DR PDBsum; 1QU6; -. DR PDBsum; 2A19; -. DR PDBsum; 2A1A; -. DR PDBsum; 3UIU; -. DR PDBsum; 6D3K; -. DR PDBsum; 6D3L; -. DR PDBsum; 7OBK; -. DR PDBsum; 7OBL; -. DR PDBsum; 8BI7; -. DR PDBsum; 8I9J; -. DR AlphaFoldDB; P19525; -. DR BMRB; P19525; -. DR EMDB; EMD-35274; -. DR SMR; P19525; -. DR BioGRID; 111596; 371. DR DIP; DIP-2657N; -. DR IntAct; P19525; 136. DR MINT; P19525; -. DR STRING; 9606.ENSP00000233057; -. DR BindingDB; P19525; -. DR ChEMBL; CHEMBL5785; -. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB07995; H-89. DR DrugBank; DB00328; Indomethacin. DR DrugCentral; P19525; -. DR GuidetoPHARMACOLOGY; 2016; -. DR GlyGen; P19525; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P19525; -. DR PhosphoSitePlus; P19525; -. DR SwissPalm; P19525; -. DR BioMuta; EIF2AK2; -. DR DMDM; 125527; -. DR EPD; P19525; -. DR jPOST; P19525; -. DR MassIVE; P19525; -. DR MaxQB; P19525; -. DR PaxDb; 9606-ENSP00000233057; -. DR PeptideAtlas; P19525; -. DR ProteomicsDB; 19391; -. DR ProteomicsDB; 53670; -. [P19525-1] DR Pumba; P19525; -. DR TopDownProteomics; P19525-1; -. [P19525-1] DR Antibodypedia; 3548; 1415 antibodies from 43 providers. DR DNASU; 5610; -. DR Ensembl; ENST00000233057.9; ENSP00000233057.4; ENSG00000055332.19. [P19525-1] DR Ensembl; ENST00000395127.6; ENSP00000378559.2; ENSG00000055332.19. [P19525-1] DR Ensembl; ENST00000405334.5; ENSP00000385014.1; ENSG00000055332.19. [P19525-2] DR Ensembl; ENST00000647926.1; ENSP00000497534.1; ENSG00000055332.19. [P19525-1] DR Ensembl; ENST00000679507.1; ENSP00000506024.1; ENSG00000055332.19. [P19525-1] DR Ensembl; ENST00000681463.1; ENSP00000505138.1; ENSG00000055332.19. [P19525-1] DR Ensembl; ENST00000681507.1; ENSP00000505772.1; ENSG00000055332.19. [P19525-1] DR GeneID; 5610; -. DR KEGG; hsa:5610; -. DR MANE-Select; ENST00000233057.9; ENSP00000233057.4; NM_001135651.3; NP_001129123.1. DR UCSC; uc010fab.3; human. [P19525-1] DR AGR; HGNC:9437; -. DR CTD; 5610; -. DR DisGeNET; 5610; -. DR GeneCards; EIF2AK2; -. DR HGNC; HGNC:9437; EIF2AK2. DR HPA; ENSG00000055332; Low tissue specificity. DR MalaCards; EIF2AK2; -. DR MIM; 176871; gene. DR MIM; 618877; phenotype. DR MIM; 619687; phenotype. DR neXtProt; NX_P19525; -. DR OpenTargets; ENSG00000055332; -. DR Orphanet; 256; Early-onset generalized limb-onset dystonia. DR PharmGKB; PA33779; -. DR VEuPathDB; HostDB:ENSG00000055332; -. DR eggNOG; KOG1033; Eukaryota. DR GeneTree; ENSGT00940000160736; -. DR HOGENOM; CLU_023682_1_0_1; -. DR InParanoid; P19525; -. DR OMA; LIQMEFC; -. DR OrthoDB; 8734at2759; -. DR PhylomeDB; P19525; -. DR TreeFam; TF317576; -. DR PathwayCommons; P19525; -. DR Reactome; R-HSA-1169408; ISG15 antiviral mechanism. DR Reactome; R-HSA-169131; Inhibition of PKR. DR Reactome; R-HSA-4755510; SUMOylation of immune response proteins. DR Reactome; R-HSA-909733; Interferon alpha/beta signaling. DR Reactome; R-HSA-9833482; PKR-mediated signaling. DR SignaLink; P19525; -. DR SIGNOR; P19525; -. DR BioGRID-ORCS; 5610; 13 hits in 1193 CRISPR screens. DR ChiTaRS; EIF2AK2; human. DR EvolutionaryTrace; P19525; -. DR GeneWiki; Protein_kinase_R; -. DR GenomeRNAi; 5610; -. DR Pharos; P19525; Tchem. DR PRO; PR:P19525; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; P19525; Protein. DR Bgee; ENSG00000055332; Expressed in endometrium epithelium and 211 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0005840; C:ribosome; TAS:AgBase. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0003725; F:double-stranded RNA binding; IDA:MGI. DR GO; GO:0004694; F:eukaryotic translation initiation factor 2alpha kinase activity; IMP:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0016301; F:kinase activity; IDA:UniProt. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:UniProtKB-EC. DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB. DR GO; GO:0019888; F:protein phosphatase regulator activity; TAS:ProtInc. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; TAS:ProtInc. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0140374; P:antiviral innate immune response; IDA:UniProt. DR GO; GO:0034198; P:cellular response to amino acid starvation; IMP:UniProtKB. DR GO; GO:0051607; P:defense response to virus; IEP:ARUK-UCL. DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IEA:Ensembl. DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl. DR GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:ProtInc. DR GO; GO:0033689; P:negative regulation of osteoblast proliferation; IMP:UniProtKB. DR GO; GO:0017148; P:negative regulation of translation; IDA:UniProtKB. DR GO; GO:0045071; P:negative regulation of viral genome replication; IMP:UniProtKB. DR GO; GO:0032722; P:positive regulation of chemokine production; ISS:UniProtKB. DR GO; GO:0001819; P:positive regulation of cytokine production; ISS:UniProtKB. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:UniProtKB. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB. DR GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; ISS:UniProtKB. DR GO; GO:0032874; P:positive regulation of stress-activated MAPK cascade; ISS:UniProtKB. DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:1901532; P:regulation of hematopoietic progenitor cell differentiation; ISS:UniProtKB. DR GO; GO:1902036; P:regulation of hematopoietic stem cell differentiation; ISS:UniProtKB. DR GO; GO:1902033; P:regulation of hematopoietic stem cell proliferation; ISS:UniProtKB. DR GO; GO:1900225; P:regulation of NLRP3 inflammasome complex assembly; ISS:UniProtKB. DR GO; GO:0035455; P:response to interferon-alpha; IDA:UniProtKB. DR GO; GO:0009615; P:response to virus; IMP:UniProtKB. DR GO; GO:0006412; P:translation; IEA:Ensembl. DR CDD; cd19903; DSRM_EIF2AK2_rpt1; 1. DR CDD; cd19904; DSRM_EIF2AK2_rpt2; 1. DR CDD; cd14047; STKc_EIF2AK2_PKR; 1. DR Gene3D; 3.30.160.20; -; 2. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR IDEAL; IID00443; -. DR InterPro; IPR014720; dsRBD_dom. DR InterPro; IPR044452; EIF2AK2_DSRM_1. DR InterPro; IPR044453; EIF2AK2_DSRM_2. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR11042; EUKARYOTIC TRANSLATION INITIATION FACTOR 2-ALPHA KINASE EIF2-ALPHA KINASE -RELATED; 1. DR PANTHER; PTHR11042:SF163; INTERFERON-INDUCED, DOUBLE-STRANDED RNA-ACTIVATED PROTEIN KINASE; 1. DR Pfam; PF00035; dsrm; 2. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00358; DSRM; 2. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF54768; dsRNA-binding domain-like; 2. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS50137; DS_RBD; 2. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; P19525; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Antiviral defense; KW ATP-binding; Cytoplasm; Direct protein sequencing; Disease variant; KW Dystonia; Host-virus interaction; Immunity; Innate immunity; KW Isopeptide bond; Kinase; Magnesium; Nucleotide-binding; Nucleus; KW Phosphoprotein; Reference proteome; Repeat; RNA-binding; KW Serine/threonine-protein kinase; Transcription; Transcription regulation; KW Transferase; Tyrosine-protein kinase; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.13, ECO:0007744|PubMed:22223895, FT ECO:0007744|PubMed:22814378" FT CHAIN 2..551 FT /note="Interferon-induced, double-stranded RNA-activated FT protein kinase" FT /id="PRO_0000085945" FT DOMAIN 9..77 FT /note="DRBM 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00266, FT ECO:0000269|PubMed:9736623" FT DOMAIN 100..167 FT /note="DRBM 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00266, FT ECO:0000269|PubMed:9736623" FT DOMAIN 267..538 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REPEAT 331..343 FT /note="1" FT REPEAT 345..357 FT /note="2" FT REGION 2..180 FT /note="(Microbial infection) Interaction with HCV NS5A" FT /evidence="ECO:0000269|PubMed:17267064" FT REGION 202..222 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 266..551 FT /note="Interaction with TRAF5" FT /evidence="ECO:0000269|PubMed:15121867" FT REGION 266..362 FT /note="Dimerization" FT /evidence="ECO:0000269|PubMed:16179258" FT REGION 331..357 FT /note="2 X 13 AA approximate repeats" FT REGION 379..496 FT /note="Interaction with EIF2S1/EIF-2ALPHA" FT /evidence="ECO:0000269|PubMed:16179258" FT ACT_SITE 414 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 273..281 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 296 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 432 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000305|PubMed:16179258, FT ECO:0000305|PubMed:31246429" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000269|Ref.13, ECO:0007744|PubMed:22223895, FT ECO:0007744|PubMed:22814378" FT MOD_RES 83 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11152499, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231" FT MOD_RES 88 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000305|PubMed:11152499" FT MOD_RES 89 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000305|PubMed:11152499" FT MOD_RES 90 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000305|PubMed:11152499" FT MOD_RES 101 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:16373505" FT MOD_RES 162 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:16373505" FT MOD_RES 242 FT /note="Phosphoserine; by autocatalysis" FT /evidence="ECO:0000305|PubMed:11152499" FT MOD_RES 255 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000305|PubMed:11152499" FT MOD_RES 258 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000305|PubMed:11152499" FT MOD_RES 293 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:16373505" FT MOD_RES 446 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:11337501, FT ECO:0000269|PubMed:16179258" FT MOD_RES 451 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:11337501, FT ECO:0000269|PubMed:20685959" FT MOD_RES 456 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 542 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CROSSLNK 69 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ISG15)" FT /evidence="ECO:0000269|PubMed:23229543" FT CROSSLNK 159 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ISG15)" FT /evidence="ECO:0000269|PubMed:23229543" FT VAR_SEQ 263..303 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.7" FT /id="VSP_046177" FT VARIANT 11 FT /note="M -> L (in LEUDEN; uncertain significance; reduced FT phosphorylation of eukaryotic translation initiation factor FT 2-alpha in patient cells)" FT /evidence="ECO:0000269|PubMed:32197074" FT /id="VAR_084260" FT VARIANT 32 FT /note="N -> S (in LEUDEN; uncertain significance)" FT /evidence="ECO:0000269|PubMed:32197074" FT /id="VAR_084261" FT VARIANT 32 FT /note="N -> T (in DYT33; uncertain significance; FT gain-of-function variant resulting in increased levels of FT phosphorylated EIF2AK2 and EIF2A in patient cells compared FT to controls)" FT /evidence="ECO:0000269|PubMed:33236446" FT /id="VAR_086715" FT VARIANT 97 FT /note="S -> F (in LEUDEN; uncertain significance)" FT /evidence="ECO:0000269|PubMed:32197074" FT /id="VAR_084262" FT VARIANT 109 FT /note="A -> S (in LEUDEN; uncertain significance)" FT /evidence="ECO:0000269|PubMed:32197074" FT /id="VAR_084263" FT VARIANT 109 FT /note="A -> V (in LEUDEN; uncertain significance)" FT /evidence="ECO:0000269|PubMed:32197074" FT /id="VAR_084264" FT VARIANT 114 FT /note="L -> Q (found in a patient with dysmorphic facies, FT syndactyly, congenital microcephaly and global FT developmental delay; uncertain significance)" FT /evidence="ECO:0000269|PubMed:32197074" FT /id="VAR_084265" FT VARIANT 130 FT /note="G -> R (in DYT33; gain-of-function variant resulting FT in increased levels of phosphorylated EIF2AK2 and EIF2A in FT patient cells compared to controls)" FT /evidence="ECO:0000269|PubMed:33236446, FT ECO:0000269|PubMed:33866603, ECO:0000269|PubMed:35146068" FT /id="VAR_086716" FT VARIANT 133 FT /note="Y -> F (in LEUDEN; uncertain significance; reduced FT phosphorylation of eukaryotic translation initiation factor FT 2-alpha in patient cells)" FT /evidence="ECO:0000269|PubMed:32197074" FT /id="VAR_084266" FT VARIANT 138 FT /note="G -> A (in DYT33; uncertain significance)" FT /evidence="ECO:0000269|PubMed:33236446" FT /id="VAR_086717" FT VARIANT 325 FT /note="G -> S (in LEUDEN; uncertain significance)" FT /evidence="ECO:0000269|PubMed:32197074" FT /id="VAR_084267" FT VARIANT 428 FT /note="V -> E (in dbSNP:rs56219559)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040474" FT VARIANT 439 FT /note="L -> V (in a lung adenocarcinoma sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040475" FT VARIANT 461 FT /note="S -> C (in LEUDEN; uncertain significance; reduced FT phosphorylation of eukaryotic translation initiation factor FT 2-alpha in patient cells)" FT /evidence="ECO:0000269|PubMed:32197074" FT /id="VAR_084268" FT VARIANT 506 FT /note="I -> V (in dbSNP:rs34821155)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040476" FT MUTAGEN 59..60 FT /note="SK->AA: In FL-PKR-2AI; moderate loss of activity but FT no effect on dsRNA binding." FT /evidence="ECO:0000269|PubMed:11337501" FT MUTAGEN 60 FT /note="K->A: Impairs dsRNA binding but not dimerization or FT activity." FT /evidence="ECO:0000269|PubMed:11337501" FT MUTAGEN 67 FT /note="A->E: Significant loss of activity; loss of dsRNA FT binding and dimerization." FT /evidence="ECO:0000269|PubMed:11337501" FT MUTAGEN 83 FT /note="S->A: No effect on enzymatic activity; when FT associated with A-88; A-89 and A-90." FT /evidence="ECO:0000269|PubMed:11152499" FT MUTAGEN 88 FT /note="T->A: No effect on enzymatic activity; when FT associated with A-83; A-89 and A-90." FT /evidence="ECO:0000269|PubMed:11152499" FT MUTAGEN 89 FT /note="T->A: No effect on enzymatic activity; when FT associated with A-83; A-88 and A-90." FT /evidence="ECO:0000269|PubMed:11152499" FT MUTAGEN 90 FT /note="T->A: No effect on enzymatic activity; when FT associated with A-83; A-88 and A-89." FT /evidence="ECO:0000269|PubMed:11152499" FT MUTAGEN 149..150 FT /note="TK->AA: In FL-PKR-2AII; no effect on activity." FT /evidence="ECO:0000269|PubMed:11337501" FT MUTAGEN 242 FT /note="S->A: Moderate loss of activity; when associated FT with A-255 and A-258." FT /evidence="ECO:0000269|PubMed:11152499" FT MUTAGEN 244..296 FT /note="Missing: Loss of activity." FT /evidence="ECO:0000269|PubMed:11337501" FT MUTAGEN 255 FT /note="T->A: Moderate loss of activity; when associated FT with A-242 and A-255." FT /evidence="ECO:0000269|PubMed:11152499" FT MUTAGEN 258 FT /note="T->A: Moderate loss of activity." FT /evidence="ECO:0000269|PubMed:11152499" FT MUTAGEN 296 FT /note="K->R: Loss of activity." FT /evidence="ECO:0000269|PubMed:11152499" FT MUTAGEN 446 FT /note="T->A: Significant loss of activity and impairs FT autophosphorylation of T-451." FT /evidence="ECO:0000269|PubMed:11337501" FT MUTAGEN 451 FT /note="T->A: Loss of activity." FT /evidence="ECO:0000269|PubMed:11337501" FT MUTAGEN 486 FT /note="D->V: 15-fold decrease in K3L binding affinity and FT thus resistance of mutated PKR to K3L inhibition." FT /evidence="ECO:0000269|PubMed:18971339" FT MUTAGEN 489 FT /note="F->S: Loss of PKR inhibition by HCMV protein TRS1." FT /evidence="ECO:0000269|PubMed:27780231" FT MUTAGEN 496 FT /note="T->K: No effect on PKR inhibition by HCMV protein FT TRS1." FT /evidence="ECO:0000269|PubMed:27780231" FT MUTAGEN 502 FT /note="I->T: No effect on PKR inhibition by HCMV protein FT TRS1." FT /evidence="ECO:0000269|PubMed:27780231" FT MUTAGEN 506 FT /note="I->V: No effect on PKR inhibition by HCMV protein FT TRS1." FT /evidence="ECO:0000269|PubMed:27780231" FT MUTAGEN 510 FT /note="K->R: No effect on PKR inhibition by HCMV protein FT TRS1." FT /evidence="ECO:0000269|PubMed:27780231" FT MUTAGEN 516 FT /note="Q->E: No effect on PKR inhibition by HCMV protein FT TRS1." FT /evidence="ECO:0000269|PubMed:27780231" FT CONFLICT 102 FT /note="I -> M (in Ref. 7; AAP57628)" FT /evidence="ECO:0000305" FT CONFLICT 224 FT /note="S -> R (in Ref. 7; AAP57628)" FT /evidence="ECO:0000305" FT CONFLICT 512 FT /note="K -> E (in Ref. 6; AAF13156)" FT /evidence="ECO:0000305" FT STRAND 5..7 FT /evidence="ECO:0007829|PDB:1QU6" FT HELIX 10..21 FT /evidence="ECO:0007829|PDB:1QU6" FT STRAND 26..32 FT /evidence="ECO:0007829|PDB:1QU6" FT TURN 35..37 FT /evidence="ECO:0007829|PDB:1QU6" FT STRAND 41..50 FT /evidence="ECO:0007829|PDB:1QU6" FT STRAND 54..56 FT /evidence="ECO:0007829|PDB:1QU6" FT HELIX 61..76 FT /evidence="ECO:0007829|PDB:1QU6" FT HELIX 102..111 FT /evidence="ECO:0007829|PDB:1QU6" FT STRAND 115..123 FT /evidence="ECO:0007829|PDB:1QU6" FT STRAND 125..138 FT /evidence="ECO:0007829|PDB:1QU6" FT STRAND 144..149 FT /evidence="ECO:0007829|PDB:1QU6" FT HELIX 150..167 FT /evidence="ECO:0007829|PDB:1QU6" FT HELIX 261..266 FT /evidence="ECO:0007829|PDB:2A19" FT STRAND 267..274 FT /evidence="ECO:0007829|PDB:2A19" FT STRAND 276..278 FT /evidence="ECO:0007829|PDB:2A19" FT STRAND 281..286 FT /evidence="ECO:0007829|PDB:2A19" FT TURN 287..289 FT /evidence="ECO:0007829|PDB:2A19" FT STRAND 292..299 FT /evidence="ECO:0007829|PDB:2A19" FT HELIX 303..305 FT /evidence="ECO:0007829|PDB:2A19" FT HELIX 306..314 FT /evidence="ECO:0007829|PDB:2A19" FT STRAND 323..332 FT /evidence="ECO:0007829|PDB:2A19" FT STRAND 358..366 FT /evidence="ECO:0007829|PDB:2A19" FT HELIX 374..380 FT /evidence="ECO:0007829|PDB:2A19" FT HELIX 381..383 FT /evidence="ECO:0007829|PDB:2A19" FT HELIX 388..407 FT /evidence="ECO:0007829|PDB:2A19" FT STRAND 410..412 FT /evidence="ECO:0007829|PDB:2A1A" FT HELIX 417..419 FT /evidence="ECO:0007829|PDB:2A19" FT STRAND 420..424 FT /evidence="ECO:0007829|PDB:2A19" FT STRAND 427..430 FT /evidence="ECO:0007829|PDB:2A19" FT HELIX 433..435 FT /evidence="ECO:0007829|PDB:6D3L" FT STRAND 437..440 FT /evidence="ECO:0007829|PDB:2A19" FT HELIX 457..461 FT /evidence="ECO:0007829|PDB:2A19" FT HELIX 468..482 FT /evidence="ECO:0007829|PDB:2A19" FT HELIX 488..499 FT /evidence="ECO:0007829|PDB:2A19" FT STRAND 505..507 FT /evidence="ECO:0007829|PDB:3UIU" FT HELIX 509..518 FT /evidence="ECO:0007829|PDB:2A19" FT HELIX 523..525 FT /evidence="ECO:0007829|PDB:2A19" FT HELIX 529..539 FT /evidence="ECO:0007829|PDB:2A19" SQ SEQUENCE 551 AA; 62094 MW; 815AD83ACAB45DA3 CRC64; MAGDLSAGFF MEELNTYRQK QGVVLKYQEL PNSGPPHDRR FTFQVIIDGR EFPEGEGRSK KEAKNAAAKL AVEILNKEKK AVSPLLLTTT NSSEGLSMGN YIGLINRIAQ KKRLTVNYEQ CASGVHGPEG FHYKCKMGQK EYSIGTGSTK QEAKQLAAKL AYLQILSEET SVKSDYLSSG SFATTCESQS NSLVTSTLAS ESSSEGDFSA DTSEINSNSD SLNSSSLLMN GLRNNQRKAK RSLAPRFDLP DMKETKYTVD KRFGMDFKEI ELIGSGGFGQ VFKAKHRIDG KTYVIKRVKY NNEKAEREVK ALAKLDHVNI VHYNGCWDGF DYDPETSDDS LESSDYDPEN SKNSSRSKTK CLFIQMEFCD KGTLEQWIEK RRGEKLDKVL ALELFEQITK GVDYIHSKKL IHRDLKPSNI FLVDTKQVKI GDFGLVTSLK NDGKRTRSKG TLRYMSPEQI SSQDYGKEVD LYALGLILAE LLHVCDTAFE TSKFFTDLRD GIISDIFDKK EKTLLQKLLS KKPEDRPNTS EILRTLTVWK KSPEKNERHT C //